Developments in diabetes management for older people 1991–2023

Abstract

The landscape of type 2 diabetes management has changed dramatically in the 32 years since Mario De Luise's 1991 Geriatric Therapeutics paper on ‘Treatment of diabetes mellitus in the elderly’.¹ As De Luise predicted, the combined effect of an ageing population and real increases in the age-specific incidence of diabetes has led to a significant impact on the healthcare system. The number of people living with diabetes in Australia increased more than 2-fold between 2001 and 2022, and almost one in five (18.7%) people aged over 75 years now has diabetes.²

Our understanding of the pathophysiology of diabetes and its complications has been enhanced by landmark trials such as the UK Prospective Diabetes Study (UKPDS), published in 1998, which challenged the thinking of the time that there was little evidence that tight glycaemic control could reduce the progression of established microvascular complications (kidney disease, retinopathy and neuropathy).³ With tight glycaemic control, however, can come harm. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, published in 2008, found that intensive therapy with drugs that cause hypoglycaemia can increase mortality in patients with, or at high risk of, cardiovascular disease.⁴ Hypoglycaemia in older people may also increase the risk of falls and has been associated with reduced quality of life.⁵

The therapeutic options for treating type 2 diabetes have expanded dramatically in the last 30 years, particularly in the second half of that period. In 1991 the available drugs were limited to sulfonylureas, metformin and insulin.¹ Dexfenfluramine, a serotoninergic anorectic drug, introduced in De Luise's paper as having a potential evolving role in the management of type 2 diabetes,¹ was later that decade withdrawn, along with fenfluramine, due to an increased risk of valvular heart disease and pulmonary hypertension. The tale of diabetes drug advances has a central theme of pharmacovigilance. In 2008 the US Food and Drug Administration issued a Guidance for Industry requiring all new type 2 diabetes drug development programs to rule out unacceptable cardiovascular risk. In part this was motivated by concern about the potential signal of an increased cardiovascular risk with the thiazolidinedione drug, rosiglitazone.⁶ Rather than dampening enthusiasm for diabetes drug development, what followed has been the approval of multiple new drugs for type 2 diabetes, including dipeptidyl peptidase-4 (DPP4) inhibitors (‘gliptins’), sodium-glucose cotransporter-2 (SGLT2) inhibitors (‘gliflozins’) and glucagon-like peptide-1 (GLP-1) receptor agonists (incretin mimetics), each with cardiovascular outcome trial data that was required to include older adults at higher risk of cardiovascular events. The landmark 2015 EMPA-REG trial (empagliflozin vs placebo in addition to standard care, mean patient age 63.1 ± 8.6 years) was the first diabetes drug trial to demonstrate a reduction in risk of cardiovascular death, hospitalisation for heart failure and death from any cause.⁷ We now have multiple diabetes drugs with established cardiovascular, renal and heart failure benefits that are independent of their glucose-lowering properties, and their indications are expanding outside of diabetes to include the management of heart failure, renal disease and obesity. These newer drugs also have the advantage of lower risk of hypoglycaemia compared to sulfonylureas and insulins, which, aside from metformin, were the only pharmacological options when De Luise's article was written in 1991.

Despite advances in understanding and the number of effective therapeutic options, there remain numerous challenges in the management of the older person with diabetes. Diabetes in the older adult is frequently associated with multimorbidity. Polypharmacy is almost unavoidable, which increases the risk of drug interactions, adverse effects and non-adherence. Some things have not changed at all since De Luise's paper was published: the key therapeutic message of the need to individualise management and therapeutic targets in the older person living with diabetes is just as important in 2023 as it was in 1991.

The author declares that he has no conflicts of interest.

This commentary received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.